Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
Metab Eng. 2011 Mar;13(2):204-13. doi: 10.1016/j.ymben.2010.12.004. Epub 2010 Dec 13.
The model-driven search for gene deletion strategies that increase the production performance of microorganisms is an essential part of metabolic engineering. One theoretical approach is based on Minimal Cut Sets (MCSs) which are minimal sets of knockouts disabling the operation of a specified set of target elementary modes. A limitation of the current approach is that MCSs can induce side effects disabling also desired functionalities. We, therefore, generalize MCSs to Constrained MCSs (cMCSs) allowing for the additional definition of a set of desired modes of which a minimum number must be preserved. Exemplarily for ethanol production by Escherichia coli, we demonstrate that this approach offers enormous flexibility in defining and solving knockout problems. Moreover, many existing methods can be reformulated as special cMCS problems. The cMCSs approach allows systematic enumeration of all equivalent gene deletion combinations and also helps to determine robust knockout strategies for coupled product and biomass synthesis.
基于模型的基因删除策略搜索是微生物生产性能提升的代谢工程的重要组成部分。一种理论方法是基于最小割集（MCS），它是禁用一组指定目标基本模式操作的最小集合。当前方法的一个局限性是，MCS 可能会产生副作用，从而禁用所需的功能。因此，我们将 MCS 推广到约束最小割集（cMCS），允许额外定义一组所需的模式，其中必须保留最小数量的模式。以大肠杆菌生产乙醇为例，我们证明了这种方法在定义和解决敲除问题方面具有巨大的灵活性。此外，许多现有的方法可以重新表述为特殊的 cMCS 问题。cMCS 方法允许系统地枚举所有等效的基因删除组合，还有助于确定耦合产物和生物量合成的稳健敲除策略。
